BDB-Lab Spring 2022 Update

Ecological Factors and Horizontal Gene Transfer by Marija Dmitrijeva

Spring 2022 Focus: Ecological Factors and Horizontal Gene Transfer by Marija Dmitrijeva

This quarter, we focus on Marija Dmitrijeva from the University of Zürich, who is a friend of our lab and has visited us in Shanghai and remotely.

What is horizontal gene transfer (HGT) and why is it important to study what influences it?

HGT is the exchange of genetic material between organisms through mechanisms other than vertical inheritance (from parent to offspring). For prokaryotes, it is a “quick” way to gain an advantageous phenotype. There’s plenty of discussion on the contribution of HGT to the spread of antibiotic resistance, but it does not need to have only negative consequences for humans. For example, a famous study from Hehemann et al. showed that gut microbiota in the Japanese population horizontally received genes coding for enzymes that help degradation of polysaccharides from the red algae commonly used in Japanese cuisine.

How do you detect HGT and link it to the species’ ecology?

For our current study, we decided to focus on comparing high-quality genomes from bacterial and archeal isolates. We generate a pangenome for each species to reduce sequence redundancy. We then create a phylogenetic tree for each group of similar genes and reconcile it with the species tree. That is, I run RANGER-DTL, a software that comes up with a possible evolutionary explanation for the differences (if any exist) between the gene tree and the species tree. By using tree reconciliation, we are able to get older transfer events than we would have from comparing the sequences directly. For the ecological profiles, I extract the 16S rRNA gene sequence from the same high-quality genomes and map it to operational taxonomic units from the Microbe Atlas Project (website in development). 

Why did you decide to focus on ecological factors in particular?

Shared ecology has been shown to play an important role in HGT. In my main lab led by Christian von Mering (University of Zurich, Swiss Bioinformatics Institute, Zurich, Switzerland), we are currently developing the Microbe Atlas Project (website in development) - an extensive dataset containing nearly two million microbiome samples. These samples have been analyzed using the same pipeline and mapped to the same reference, allowing comparison between different studies and projects. Using this dataset, I can not only look for whether two bacteria participating in HGT occur in the same type of environment, but track their presence/absence and abundances across thousands of samples.

The Microbe Atlas Project - exploring the microbiome of the world. Over 3.5 million samples dating up to January 2021 have been downloaded from the Sequence Read Archive and analyzed, resulting in 1.9 environmental sequencing samples available for comparison. Figure kindly provided by João Matias Rodrigues.

Can you tell us a bit about yourself: what was your path to get here?

Originally I’m from Riga, Latvia. After finishing school, I moved to Vlissingen (a small coastal city in the south of the Netherlands) to study chemistry and molecular life sciences. Somewhere along the way I realized that I had way more fun with bioinformatics than with working in the wet lab. I therefore obtained a Masters in Bioinformatics from Vrije Universiteit Amsterdam, writing my thesis on DNA methylation in aging and cancer at the lab of Luis Serrano (Center for Genomic Regulation, Barcelona, Spain). Afterwards I moved to the University of Zurich in Switzerland to start my PhD in the lab of Christian von Mering. I switched my research focus from epigenetics and cancer to microbiomes and took over a clinical collaboration using metagenomics to study pathogens in cystic fibrosis patients. Luis and I met at The Human Microbiome Symposium, where I expressed interest in visiting his lab and taking on a project analyzing data on a global scale. The visit itself had to be cut short in 2020, but we have been successfully developing this project remotely since then!

What are your future (scientific) plans?

First and foremost I would like to defend my PhD later this year. I’m working hard on finalizing the analysis for the association between ecological factors and HGT and hope to start writing the manuscript soon. As for my life post-PhD, I am currently exploring the options. Microbiome research excites me and I would like to continue in the field and use my bioinformatics skills to help people gain insights into microbiomes of all shapes and sizes. I’m also starting to miss the environment of the biotech start-up that I worked for after my Bachelor’s and during my Master’s - I found working on the development of novel therapies extremely rewarding. I am currently helping organize the Swiss Microbiomes Forum - an on-site event in Lausanne showcasing industry, start-ups and organizations in Switzerland focusing on microbiome-based solutions. I hope to get some inspiration there and I invite you to register if you are in the area!

How can people find more updates on your research?

You can find a list of all my publications on Google Scholar. Also feel free to reach out to me via e-mail (marija.dmitrijeva@mls.uzh.ch), I’m always happy to schedule a chat.

Other BDB-Lab Updates

Manuscripts

Several manuscripts we collaborated on were published recently:

• Supriya Khedkar, et al. Landscape of mobile genetic elements and their antibiotic resistance cargo in prokaryotic genomes, Nucleic Acids Research

• Boas C.L. van der Putten, C. I. Mendes, et al. Software testing in microbial bioinformatics: a call to action. Microbial Genomics

• Fromentin S, Forslund SK, Chechi K et al. Microbiome and metabolome features of the cardiometabolic disease spectrum. Nature Medicine

• Belda E, Voland L, Tremaroli V, et al. Impairment of gut microbial biotin metabolism and host biotin status in severe obesity: effect of biotin and prebiotic supplementation on improved metabolism. Gut (2022)

Preprints:

• Hui Chong, Qingyang Yu, Yuguo Zha, Guangzhou Xiong, Nan Wang, Xinhe Huang, Shijuan Huang, Chuqing Sun, Sicheng Wu, Wei-Hua Chen, Luis Pedro Coelho, Kang Ning. EXPERT: Transfer Learning-enabled context-aware microbial source tracking. bioRxiv

• Álvaro Rodríguez del Río, Joaquín Giner-Lamia, Carlos P. Cantalapiedra, Jorge Botas, Ziqi Deng, Ana Hernández-Plaza, Lucas Paoli, Thomas S.B. Schmidt, Shinichi Sunagawa, Peer Bork, Luis Pedro Coelho, Jaime Huerta-Cepas. Functional and evolutionary significance of unknown genes from uncultivated taxa. bioRxiv

We are also optimistic that the SemiBin manuscript will be out soon (preprint here: 10.1101/2021.08.16.456517v1).

Tutorial. We started a code club, follow this link for more information.

Online resources & tools. SemiBin had constant updates, with a release (0.6) in February and another (0.7) in March. The results should be similar, but the tool is becoming more robust and polished. This includes the more efficient code presented at our code club. We also expanded the set of habitats where pretrained models are available to ten.

Svetlana has been curating a beginner guide with learning online resources related to microbiome computational science and tools.

Other. Svetlana joined ​​the Australasian Human Microbiome Research Network. 

Svetlana and Anna joined the Network of European Researchers in Biology and Medicine in China.

New remote interns

The end of February was our deadline for remote interns and we have gotten 34 applications. We would like to introduce our new interns for this Spring and Summer:

Jelena Somborski (fairyhel@gmail.com, https://github.com/fairyhel, https://twitter.com/fairyhel023 ): I hold a MSc in Biology, majoring in Microbiology. Being equally fascinated with living organisms and machines, I am interested in expanding my knowledge of microorganisms as well as in learning computational biology and its tools. 

Long walks in the woods, volunteering, practicing yoga, drawing, and digital painting are some of my favorite pastimes. I am also interested in foreign languages and cultures. 

Breno Livio (brenoslivio@usp.br, https://github.com/brenoslivio): I am a Computer Science undergraduate at the University of São Paulo in São Carlos, Brazil. Having studied data science subjects like Machine Learning and Statistics, I've become eager to apply the knowledge in interdisciplinary areas like Bioinformatics given its intrinsic challenges and fascinating topics such as the microbiome. In the future, I intend to pursue a graduate program in computer science with research applied to computational biology. In my spare time, I like to exercise (running, weightlifting, calisthenics), meditate, play the electric guitar, listen to 70's rock songs, and learn new things.

Looking Forward

During March and April, Svetlana will give a lecture “Exploring the global resistome within the EMBARK project” and а workshop ”Intro to bioinformatics” at the University of Novi Sad (Novi Sad, Serbia).

Svetlana will present her work on “Challenges in the metagenomic annotation of antibiotic resistome” at the Antimicrobial Resistance – Genomes, Big Data and Emerging Technologies and FEMS Conference on Microbiology.